Limb outgrowth and morphogenesis is under the control of a complex set of tissue interactions. In the chick the ectodermal ridge is known to be necessary for continued limb outgrowth but the asymmetry of its thickness and inductive activity is under the control of the mesoderm. This pattern of ridge maintenance in the mesoderm is thus reflected in the ectodermal ridge and therefore in outgrowth under the ridge's influence. The pattern of mesodermal maintenance of ectodermal ridge seems to be under the control of yet another region of the limb mesoderm, the zone of polarizing activity, which under appropriate experimental conditions will induce limb outgrowth and determine a morphogenetic pattern - the anteroposterior polarity of the induced limb. The object of this proposed research is to investigate the mechanisms involved in these interactions using microsurgical and in vitro culture techniques. The nature of the morphogenetic substances will also be investigated. In addition the alteration of these interactions in polydactylous limbs of the chick and mouse will be examined.